One third or more of HIV infections in breastfeeding infants are acquired from mother's milk. When economically possible, formula feeding has been suggested as an alternative to breastfeeding for infants born to HIV positive mothers. At the same time, an absence of breastfeeding is likely to increase infant morbidity and mortality, especially in environments where water quality and sewage treatment are not optimal. When zidovudine (ZDV) is given to HIV-infected pregnant mothers for at least four weeks prior to birth it can reduce the rate of in utero and/or perinatal infections by 50 percent or more. Similarly, when nevirapine (NVP) was given to HIV positive mothers during labor and to newborn infants in Uganda it significantly reduced neonatal infections with HIV. We propose a trial with a factorial design to compare breastfeeding with infant ZDV chemoprophylaxis to formula feeding. In the same population we would also compare six weeks of maternal prenatal ZDV plus a dose of maternal NVP during labor and a dose of neonatal NVP within 24 hours after birth. The trial is proposed for Botswana, where the Ministry of Health initiated a feasibility program, beginning in May 1999, to administer six weeks of prenatal ZDV and six months of infant formula feeding to 400 HIV positive women and their infants. In Botswana, the HIV infection rate of pregnant women is estimated to be 38.5 percent. Almost all HIV infections in Botswana are subtype HIV-1C, which has rapidly expanded to account for more than half of the world's HIV infections. Additionally, when compared to other subtypes in Africa, HIV-1C has been found to have elevated rates of mother-to-child transmission (MTCT) and elevated rates of transmission through breast milk.